Large scale grids for in silico drug discovery open opportunities of particular interest to neglected and emerging diseases. In 2005 and 2006, we have been able to deploy large scale virtual docking within the framework of the WISDOM initiative against malaria and avian influenza requiring about 100 years of CPU on the EGEE, Auvergrid and TWGrid infrastructures. These achievements demonstrated ...

Protein kinase B (PKB/AKT) is an attractive therapeutic target in anticancer drug development. We have recently identified by docking-based virtual screening a low micromolar AKT-2 inhibitor. Additionally, the virtual screening hit represents a novel AKT-2 inhibitor scaffold. In this work, we discuss a structure-based design strategy toward the optimization of this hit. Following this strategy ...

Cell cycle inhibition is important hallmark of anti cancer research. CDKs are divided into two types based on their Cell cycle controlling and transcriptional control. CDK 9, a transcriptional regulator serves as potential drug target. Only few drugs are under clinical trials phase 1/2/3 of CDK 9 inhibitory potential. 3BLR (pdb id) is used as docking target. Virtual screening is carried out bas...

Multitarget agents have been extensively explored for solving limited efficacies, poor safety, and resistant profiles of an individual target. Theoretical approaches for searching and designing multitarget agents are critically useful. Here, the performance of molecular docking to search dual-target inhibitors for four kinase pairs (CDK2-GSK3B, EGFR-Src, Lck-Src, and Lck-VEGFR2) was assessed. F...

Web-based user interfaces to scientific applications are important tools that allow researchers to utilize a broad range of software packages with just an Internet connection and a browser. One such interface, CHARMMing (CHARMM interface and graphics), facilitates access to the powerful and widely used molecular software package CHARMM. CHARMMing incorporates tasks such as molecular structure a...

Visual haptic-based biomolecular docking systems could be used for both research and e-learning in research intensive disciplines such as biology, physical chemistry, molecular medicine, biophysics, structural biology, bioinformatics, etc. The assembly of molecules in a three-dimensional space or molecular docking is used for rational drug design where a ligand docks onto a receptor. The comput...

A combination of protein-ligand docking and ligand-based QSAR approaches has been elaborated, aiming to speed-up the process of virtual screening. In particular, this approach utilizes docking scores generated for already processed compounds to build predictive QSAR models that, in turn, assess hypothetical target binding affinities for yet undocked entries. The "progressive docking" has been t...

BEAR (Binding Estimation After Refinement) is a computational method for structure-based virtual screening. It was set up as a post-docking processing tool for the refinement of ligand binding modes predicted by molecular docking programs and the accurate evaluation of free energies of binding. BEAR has been validated in a number of computational drug discovery applications. It performed well i...

BACKGROUND Virtual (computational) screening is an increasingly important tool for drug discovery. AutoDock is a popular open-source application for performing molecular docking, the prediction of ligand-receptor interactions. AutoDock is a serial application, though several previous efforts have parallelized various aspects of the program. In this paper, we report on a multi-level parallelizat...

We have developed a new tool for virtual database screening. This tool, referred to as the Generic Evolutionary Method for molecular DOCKing (GEMDOCK), combines an evolutionary approach and a new pharmacophore-based scoring function. The former integrates discrete and continuous global search strategies with local search strategies to speed up convergence. The latter simultaneously serves as th...